Tyrosine kinase is an enzyme which phosphorylates tyrosine residues in substrate proteins, and is known to play an important role in an intracellular signal transduction system concerning cellular differentiation and proliferation. Two receptor tyrosine kinases, EGF receptor (hereinafter EGFR) and HER2 (also called ErbB2 or Neu) are considerably involved in cancer development, and their activities are increased in a variety of human cancers (Non-Patent Literature 1, Non-Patent Literature 2 and Non-Patent Literature 3). It is also shown that these kinases are aberrantly expressed in cancers of brain, lung, stomach, intestine, pancreas, head and neck part, esophagus, bladder, kidney, prostate, ovary, breast, uterine, and thyroid gland (Non-Patent Literature 4 and Patent Literature 1). Therefore, it is thought that an inhibitor of these kinases is useful as an anti-cancer drug which can be efficacious in many types of cancers and has little side effect. As the tyrosine kinase inhibitor, compounds described in Patent Literature 2, Patent Literature 3, Patent Literature 4, Patent Literature 5, Patent Literature 6, Patent Literature 7 are known.
In addition, it is known that cellular transformation due to EGFR is accelerated by additional coexpression of HER2 (Non-Patent Literature 5). Further, concomitant expression of EGFR and HER2 is reported as a marker of poor prognosis in breast, oral cavity and lung cancers (Non-Patent Literature 6). As a drug which inhibits both EGFR and HER2, compounds described in Patent Literature 8 are known.
An anti-cancer agent having an oxime-type substituent at a 4-position of a quinazoline derivative is described in Patent Literature 9 and Patent Literature 10.    [Patent Literature 1] Japanese Patent Application Laid-Open (JP-A)    [Patent Literature 2] WO 92/20642    [Patent Literature 3] EPA No. 92305703.8    [Patent Literature 4] EPA No. 0566266    [Patent Literature 5] EPA No. 0602851.    [Patent Literature 6] EPA No. 0520722    [Patent Literature 7] WO 98/02434    [Patent Literature 8] WO 02/066445    [Patent Literature 9] WO 2004/0691545    [Patent Literature 10] WO 2004/105765    [Non-Patent Literature 1] Cancer Res., 1991, vol. 51, p. 4430-4435    [Non-Patent Literature 2] Cancer Res., 1992, vol. 52, p. 3636-3641    [Non-Patent Literature 3] Cancer Chemother. Pharmacol., 1993, vol. 32, p. 1-19    [Non-Patent Literature 4] Expart. Opin. Invest. Drugs, 1994, vol. 3, No. 6,    [Non-Patent Literature 5] Cell, 1987, vol. 58, p. 287-292    [Non-Patent Literature 6] Clin. Cancer Res., 1999, vol. 5, p. 4164-4174